The cAMP-dependent protein kinase (PKA) plays an important role in cellular signal transduction and functions by transferring a phosphate from ATP to its substrate. Since aberrant kinase activity has been linked to cancer and other disease states, there are great efforts to design specific, potent inhibitors of the various kinases. PKA consists of two regulatory subunits and two catalytic subunits (rC) and upon binding the second messenger, cAMP, two rCs dissociate from the complex. rC is highly conserved (residues 40-300) among members of the protein kinase family, and as one of the simpler members, PKA serves as a prototype. Three data sets for rC have been collected at SSRL on beam lines 7-1 and 9-1: 1) apoenzyme rC - peak II (apo2) which has three phosphorylation sites - 3 E . 2) apoenzyme rC - peak III (apo3) which has two phosphorylation sites - 2.6 E . 3) balanol analog bound to rC (BD2) - 2.1 E. The apoenzyme structures are important for understanding the structural differences between the liganded and the unliganded rC forms and for studying domain movements necessary for ligand binding. The structure of BD2 reveals how rC complexes with an analog of a natural product inhibitor (IC50 0.015uM). The three structures will provide further insight to ligand binding by rC and the details regarding the active site residues involved in ligand recognition will facilitate the design of more potent and selective inhibitors of PKA for therapeutic use.